The goal of this project is to identify Borrelial and host-specific factors involved in the invasion of and persistence within the central nervous system (CNS). This will be done by identifying those strains of B. burgdorferi which are neurotropic; by determining strain antigenic variation associated with neurotropism and persistence; by defining the relationship between neurotropism ,antigenic variability, and early and late neurologic Lyme syndromes; and by examining the role of host T-cell responses in dissemination and perpetuation-of disease. This project will use erythema migrans skin biopsy, cerebrospinal fluid, and blood samples from early Lyme disease patients (Project 2), and cerebrospinal fluid and blood samples from late Lyme disease patients (Project 3). Techniques to be used include polymerase chain reaction (PCR), single-stranded conformational polymorphism and cytokine assays. The following specific aims will be addressed. Specific Aim 1: To identify neurotropic strains of B. burgdorferi. Specific Aim 2: To test the hypothesis that T-cell cytokine production (Th1 vs Th2) in response to B. burgdorferi, correlates with clinical outcome. The following predictions will be tested: A. Early Lyme patients show a predominant Th2 T-cell response, while late/chronic Lyme patients show a predominant Th1 response. B. Early Lyme patients with a predominant Th1 T-cell response are more likely to develop chronic sequelae than early Lyme disease patients with a predominant Th2 response. This will be tested by correlating cytokine production of early Lyme disease patients with clinical outcome at 18 months. C. Early Lyme patients with neurologic symptoms have a predominant Th1 response, while early Lyme patients with a single lesion of erythema migrans and no systemic symptoms have a predominant Th2 response.